Can you stop one antidepressant and start another the next day?

Sometimes. A 2016 Australian Prescriber review calls this a direct switch and says it is feasible only in selected cases, such as a change between two short half-life SSRIs. It is never used with MAOIs. Your prescriber decides if it fits your two medicines.

How long is the washout between an MAOI and an SSRI?

FDA labels for sertraline and phenelzine say at least 14 days in either direction. Fluoxetine is the exception. The Prozac label says to wait at least 5 weeks after fluoxetine before an MAOI starts.

Why does Prozac need a longer gap than other SSRIs?

It leaves the body slowly. The FDA label gives a half-life of 4 to 6 days for fluoxetine after long-term use and 4 to 16 days for its active breakdown product, norfluoxetine. The label says dose changes are not fully reflected in the blood for several weeks.

What does serotonin syndrome feel like during a medication switch?

FDA labels list agitation, a fast heartbeat, sweating, a high temperature, tremor, muscle stiffness, nausea, and diarrhea. Severe cases can include delirium and seizures. The condition can be life-threatening, so get emergency care if these signs appear.

Is it better to switch antidepressants or add a second medicine?

Trials show small differences. In the VAST-D trial of 1,522 veterans, remission at 12 weeks was 22.3% with a switch to bupropion and 28.9% with added aripiprazole, which caused more sleepiness, restlessness, and weight gain. A 2018 meta-analysis found that a switch was not superior to continued use of the first antidepressant.

How Do Doctors Switch You From One Antidepressant to Another?

The short answer: Your prescriber picks one of a few set methods. They are a direct switch, a cross-taper, or a taper followed by a drug-free gap called a washout. The choice depends on the two drugs. Most switches are simple, but a switch to or from an MAOI needs a washout of at least 14 days on FDA labels. A switch from fluoxetine (Prozac) to an MAOI needs at least 5 weeks.

When do doctors consider switching antidepressants?

There are two main reasons. A 2016 review in Australian Prescriber names them: the response to treatment is inadequate, or the side effects are unacceptable.

A switch is one option among several. The NICE depression guideline covers people whose depression had no response or a limited response to an antidepressant. It tells clinicians to first look for an obvious cause that can be resolved. Then it lists these options for a shared decision:

Increase the dose of the current medicine, if you tolerate it well.
Switch to another medicine in the same class, for example another SSRI.
Switch to a medicine in a different class, for example an SNRI.
Switch to a psychological therapy, or combine therapy and medicine.
Add a group exercise program.

Timing matters too. Our guide to how long antidepressants take to work explains how long a fair trial lasts.

What are the ways to switch from one antidepressant to another?

The Australian Prescriber review describes four methods.

Conservative switch (taper, then washout). The first drug is reduced gradually and stopped. A drug-free gap of five half-lives of the first drug follows. Then the new drug starts. The risk of a drug interaction is very low, but discontinuation symptoms can occur.
Moderate switch. The first drug is reduced gradually and stopped. The drug-free gap is 2 to 4 days. The new drug starts at a low dose.
Direct switch. The first drug is stopped, and the second drug starts the next day at its usual dose. It is quick and simple. The review says it is feasible only in selected cases, such as a change from one short half-life SSRI to another.
Cross-taper. The dose of the first drug goes down while the second drug starts at a low dose. You take both drugs for a time. The review says doctors often use this method when a relapse would be high risk.

The review calls the conservative and moderate methods suitable for general practice. It says direct and cross-taper switches need considerable expertise. It also says the dose is usually tapered over about four weeks, and that the time frame may change with patient factors.

Your prescriber sets the schedule. It depends on both drugs, your dose, and how you handled earlier dose changes.

Why do some switches need a washout?

Some drug pairs are dangerous together. The washout lets the first drug leave your body before the second drug starts.

MAOIs. Monoamine oxidase inhibitors, such as phenelzine (Nardil), are older antidepressants. The FDA label for Nardil reports serious reactions, including death, when serotonin drugs were combined with an MAOI. It says the combination is contraindicated. The FDA label for sertraline (Zoloft) says at least 14 days must pass between an MAOI antidepressant and sertraline, in either direction. The four switch methods above do not apply to MAOIs.

Fluoxetine. Fluoxetine leaves the body slowly. The FDA label for Prozac gives a half-life of 4 to 6 days for fluoxetine after long-term use. Its active breakdown product, norfluoxetine, has a half-life of 4 to 16 days. The label says dose changes are not fully reflected in the blood for several weeks. For that reason the label gives two different gaps:

At least 14 days between the end of an MAOI and the start of fluoxetine.
At least 5 weeks between the end of fluoxetine and the start of an MAOI.

For comparison, the Australian Prescriber review lists half-lives of about 1 to 1.5 days for sertraline, citalopram, escitalopram, and paroxetine. The NICE guideline adds that a switch to or from an MAOI needs specialist care or specialist advice.

What are the risks during a switch?

There are three: too much serotonin, discontinuation symptoms, and a return of depression.

Serotonin syndrome. This can occur when two serotonin drugs overlap. The Zoloft label calls it potentially life-threatening. The label lists these signs:

Mental changes: agitation, hallucinations, delirium.
Body changes: fast heartbeat, unstable blood pressure, sweating, flushing, high temperature.
Muscle changes: tremor, stiffness, jerking movements, poor coordination.
Stomach symptoms: nausea, vomiting, diarrhea.

The label says the risk is higher with other serotonin drugs. Its list includes triptans, tramadol, lithium, buspirone, and St. John's wort. Tell your prescriber about every medicine and supplement you take. Get emergency care if these signs appear during a switch.

Discontinuation symptoms. The Prozac label lists symptoms reported after SSRIs and SNRIs are stopped, particularly when the stop is abrupt. They include irritability, dizziness, electric shock sensations, anxiety, headache, and insomnia. The label recommends a gradual dose reduction whenever possible. It also says fluoxetine levels fall slowly, which may lower this risk for fluoxetine. Our guide to what happens when you stop taking antidepressants covers these symptoms in detail.

Relapse. The Australian Prescriber review warns that a conservative switch can take a long time and can include days with no treatment. Depression can worsen in that gap. The review says all switches need close observation.

One more check applies to any new antidepressant. The Zoloft label tells doctors to screen for a personal or family history of bipolar disorder, mania, or hypomania before treatment starts. bipolar.md explains those conditions.

Does switching antidepressants work?

It helps some people. The evidence does not show that a switch is better than the other next steps.

STAR*D. This large United States study tested next steps after the SSRI citalopram failed. In the switch arm, 727 adults were randomly assigned to bupropion, sertraline, or venlafaxine. Remission rates on the main scale were 21.3%, 17.6%, and 24.8%. The three drugs did not differ significantly. The authors concluded that about one in four patients had a remission after a switch.

In the augmentation arm, 565 adults kept citalopram and added bupropion or buspirone. Remission rates on the same scale were 29.7% and 30.1%. The two reports are separate, so these numbers are not a direct test of switch against add-on.

VAST-D. The VAST-D trial made that direct test in 1,522 veterans. Remission at 12 weeks was 22.3% with a switch to bupropion, 26.9% with added bupropion, and 28.9% with added aripiprazole. Only the aripiprazole result was significantly better than the switch. The authors called the gain modest. Sleepiness, restlessness, and weight gain were more frequent with aripiprazole. The group was 85.2% men, so the results may not apply to everyone.

Switch or stay. A 2018 meta-analysis compared a switch with continued use of the first antidepressant. It found 4 trials for its strict analysis and 8 for its broad analysis. A switch was not superior in either analysis.

A switch is a reasonable step, but it is not the only one. Our guide to treatment-resistant depression covers what comes after two medicines fail.

What should you ask your prescriber before a switch?

Which method will we use, and why?
Will there be days when I take no antidepressant?
Which symptoms mean I should call you, and which mean emergency care?
Do any of my other medicines or supplements raise serotonin?
When will we check if the new medicine works?

Do not change doses by yourself.

The bottom line

Doctors switch antidepressants with a direct switch, a cross-taper, or a taper with a washout. The two drugs decide the method. MAOIs and fluoxetine need the longest gaps: at least 14 days around an MAOI, and at least 5 weeks from fluoxetine to an MAOI. The main risks are serotonin syndrome, discontinuation symptoms, and relapse. About one in four people in STAR*D reached remission after a switch, and add-on treatment did about as well or slightly better in VAST-D. If you have thoughts of suicide, call or text 988 in the United States.

Last updated: October 2026. This article is for informational purposes only and does not constitute medical advice. Talk with your prescriber before you start, stop, or switch any antidepressant.